CoreB(AnimalComponent)-ProjectSummary AllresearchprojectsofthisProgramProject(PP)willrelyontheuseofgeneticallyengineeredmouse(GEM) modelstoinvestigatetherolesandmechanismofNuclearReceptors,transcriptionfactorsandtheircoregulators inenergyandmetabolichomeostasisanddisease.Morespecifically,atleast34GEMmouselineswillbeused, andthousandsofmaleandfemalemicewillbeproducedbybreedinginhouseduringthefundingperiodofthis PP.Therefore,thisAnimalComponentofCoreBisessentialforthesuccessofthisPPbyintegratingexpensive equipment, advanced technology, experienced personnel and animal resources. As shown by preliminary studies,CoreBhasgenerated/establishedmultipleGEMlinesanddevelopedCRISPR-Cas9-mediatedmouse geneeditingsystems.CoreBisdedicatedtoachieving3majorobjectives.Firstly,CoreBwilluseitsspecialized expertise, state-of-the-art equipment and adequate facilities to generate GEM lines for all investigators of this PP.CoreBhasestablishedthenecessarymethodstoeditthemousegenomebyhomologousrecombination- based gene targeting in ES cells or CRISPR/Cas9-based gene editing in 1-cell mouse embryos. Core B will generateallGEMlinesneededbytheinvestigatorsofthisPP.Secondly,CoreBwillprovidehighqualitymouse services to manage GEM line colonies and produce genotype-defined and age/sex-matched mice for all investigatorsofthisPP.Specifically,CoreBwillbreedandmaintainallofthe34mouselinesusedbythisPP. CoreBwilluseourcolonyexpansionprotocoltoproducelargenumbersofgenotype/age/sex-matchedmicefor experimental analysis. Core B also will perform genotype analysis, super ovulation, embryo and sperm cryopreservation,andinvitrofertilizationservicestohelptheinvestigatorsofthisPPformanagingtheirmouse colonies, preserving GEM lines, transferring mouse lines between institutes, and saving animal husbandry expenses. Finally, Core B will integrate the efficient usage of animal resources by all investigators of this PP. Becauseofthelarge-scaleoperationofmousemodelsandthesharingfeaturesofmultiplemouselinesamong the projects of this PP, centralized integration of equipment, expertise and valuable mouse resource will be essential for both scientific success and cost effectiveness. Core B will minimize the expenses of animal experiments by consolidating the usage and management of equipment, expertise, animal facility, mouse maintenanceandproduction.Inaddition,CoreBwillserveasaresourceforexecutionandtechnicaltrainingin theuseofallanimalmanipulationsneededandoverseethecareanduseofexperimentalmiceforthisPP.